@misc{10481/51264,
year = {2018},
month = {3},
url = {http://hdl.handle.net/10481/51264},
abstract = {Hemolytic or hemorrhagic episodes are often associated with inflammation even when infectious agents are absent suggesting that red blood cells (RBCs) release damage-associated molecular patterns (DAMPs). DAMPs activate immune and nonimmune cells through pattern recognition receptors. Heme, released from RBCs, is a DAMP and induces IL-1β production through the
activation of the nucleotide-binding domain and leucine-rich repeat-containing family and pyrin domain containing 3 (NLRP3)
in macrophages; however, other cellular targets of heme-mediated inflammasome activation were not investigated. Because of
their location, endothelial cells can be largely exposed to RBC-derived DAMPs; therefore, we investigated whether heme and
other hemoglobin- (Hb-) derived species induce NLRP3 inflammasome activation in these cells. We found that heme
upregulated NLRP3 expression and induced active IL-1β production in human umbilical vein endothelial cells (HUVECs). LPS
priming largely amplified the heme-mediated production of IL-1β. Heme administration into C57BL/6 mice induced caspase-1
activation and cleavage of IL-1β which was not observed in NLRP3−/− mice. Unfettered production of reactive oxygen species
played a critical role in heme-mediated NLRP3 activation. Activation of NLRP3 by heme required structural integrity of the
heme molecule, as neither protoporphyrin IX nor iron-induced IL-1β production. Neither naive nor oxidized forms of Hb were
able to induce IL-1β production in HUVECs. Our results identified endothelial cells as a target of heme-mediated NLRP3
activation that can contribute to the inflammation triggered by sterile hemolysis. Thus, understanding the characteristics and
cellular counterparts of RBC-derived DAMPs might allow us to identify new therapeutic targets for hemolytic diseases.},
organization = {This work was supported by grant fromthe National Research,
Development and Innovation Office (NKFIH) Grant no.
K116024. The work was cofinanced by the European Union
and the European Social Fund under the GINOP-2.3.2-15-
2016-00005 project.},
publisher = {Hindawi Publishing Corporation},
title = {Induction of NLRP3 Inflammasome Activation by Heme in Human Endothelial Cells},
doi = {doi.org/10.1155/2018/4310816},
author = {Erdei, Judit and Tóth, Andrea and Enikő, Balogh and Nyakundi, Benard Bogonko and Bányai, Emese and Ryffel, Bernhard and Paragh, György and Cordero, Mario and Jeney, Viktória},
}